Novel 17alpha-trifluoro-propynyl androstenes and processes



hates 3,046,273 NGVEL l'M-TRWLUURU-PROPYNYL AN- DRTENES AND PRESSFESJohn Fried, Plainfield, and Thomas S. Bry, Roselle, Nah, assignors toMerck it Co, Inc, Rahway, N.J., a corporation of New Jersey No Drawing.Filed Jan. 18, 1961, Ser. No. 83,389 28 Claims. (Cl. 260-23955) It hasbeen found that the above starting material will react withtrifluoropropyne, previously treated with magnesium ethyl bromide, toform the 17a-trifiuoropropynyl- 3-methoxy-2,5(10)-androstadiene-17,8-olwhich has the following structural formula:

no ego-or,

The 17e-trifluoropropynyl-3-methoxy 2,5.(10)-androstadiene-l 15-01 isconverted into the 17atrifluoropropynyl-17,8-hydroxy-19-nor-4-androstene6-one (i.e. the 21-tri- CH30 Ifluoromethyl-norethisterone) which has the following for mula.

Ho 050- F3 by reaction with a strong mineral acid, such asp-toluenesulfonic acid. For example, a mixture of the steroid andp-toluenesulfonic acid in acetone solution is left standing at roomtemperature for about 18 hours.

The 17 ot-trifluoropropynyl- 17 fi-hydroxy-l 9-nor-4-androstene-3-one isconverted into the 17,8-alkanoyl ester by reaction with an alkonic acidanhydride or alkonyl halide in the presence of a tertiary amine such aspyridine.

atent The acid anhydrides which may be used for this purpose includeacetic anhydride, propionic anhydride, butyric anhydride and the like.The 17(3-caproate is prepared by the reaction of the ZLB-free alcoholwith caproyl halide 5 in the presence of a tertiary amine base.

The l7a-trifluoropropynyl-17,6-alkoxy-l9-nor-4-androstene-S-one isprepared by reaction of the 17B-hydroxy compound with an alkyl halideand silver oxide in a solvent such as dimethylformamide. The alkylhalides which 10 may be used for this purpose include methyl iodide,ethyl iodide, n-propyl iodide, n-butyl iodide and the like.

The above l7fi-hydroxy-, 17,6-alkoxyor l73-a1kanoyloxy-l7ot-trifluoropropynyl l9'-nor-4-androstene-3-one ishydrogenated to the 17a-(3,3',3'-trifluoropropynyl)47/3-hydroxy-19-nor-4-androstene-3-one (I) using a Lindlar catalyst (leaddeactivated palladium on a calcium carbonate support), and to the17a-(3,3',3'-=trifluoropropyl)- 19-nor-4-androstene-3-one (H) using aplatinum oxide catalyst.

20 R0 oH=oHcF \i" H I R0 ornomer. V

HO CEC-C F3 Riowherein R stands for an alkyl group, are prepared bystirring together a mixture of the steroid and an alkyl orthoformate indioxane solution in the presence of a strong acid catalyst such asmineral acid, or an organic sulfonic acid. In the reaction, the17,8-alkoxyor the 17palkanoyloxy derivative may be used in place of the17B- hydroxy-cornpound to obtain the corresponding 17,8-alkoxyor17fi-alkanoyloxy derivatives.

In a preferred embodiment of our invention, the novel 3-enol ethyl etherof the 17a-trifluoropropynyl-l7fi-hydroxy-19-nor-4-androstene-3-one isprepared by adding ethyl orthoformate and p-toluenesulfonic acid to asolution of the steroidin dioxane and stirring together at roomtemperature. The acid catalyst is then neutralized with a base such aspyridine. The 3-enol n-butyl ether of the 17m-trifiuoropropynyl-17flhydroxy-l9-nor-4-androno [GEO-07F:

wherein R represents hydrogen, alkoxy or alkanoyloxy.

In a preferred embodiment of our invention, a solution of the steroidand sodium acetate in aqueous acetone is stirred withN-bromosuceinirnide and acetic acid at about C.

The 6-bromo-derivative is then dehydrogenated at A to form thel7ot-trifiuoropropynyl-l7fi-hydroxy-(17B-alkoxyor 17,8-alkanoyloxy) 19nor-4,6-androstadiene-3- one which has the structure:

wherein R is hydrogen, alkoxy or alkanoyloxy. The dehydrogenation isbrought about by heating a solution of the steroid in a solvent such asdimethyltormamide with lithium bromide and lithium carbonate for severalhours at about 120 C.

The above compound is then oxidized to the 6ot,7uepoxy 170atrifluoropropynyl-17B-hydroxy-(17B-alkoxyor 17B-alkanoyloxy)-l9-nor-4-androstene-3-one which has the followingstructure:

wherein R is hydrogen, alkoxy or alkanoyloxy, suitably by treating asolution of the steroid in a solvent such as benzene with perbenzoicacid in the dark at room temperature for about 60-70 hours.

A solution, of 6a,7u-epoxy-17a-trifluoropropynyl-17,8- hydroxy'(l7fi-alkoxyor 17,8-alkanoyloxy)-l9-nor-4- androstene-S-one in anorganic solvent is treated with HCl at room temperature to form the6-chloro-17oc-trifluoropropynyl 17B hydroxy-(17fi-alkanoxyor17fl-alkanoyl- 4 oxy)-19-nor-4,6-androstadiene-3-one which has thefollowing formula:

Cl wherein R is hydrogen, alkoxy or alkanoyloxy.

The l7a-trifluoropropynyl 3 methoxy-2,5 l0)-androstadiene 17B 01 isconverted into the17u-triiluoroprcpynyl-l7fi-hydroxy-5(lO)-androstene-3-one which has thefollowing formula:

by reaction with a weak organic acid such as acetic acid. For example, amixture of the steriod and glacial acetic acid in an aqueous solution ofabsolute ethanol and dioxane is left standing at room temperature forseveral hours.

The 17a-trifluoropropynyl 17B hydroxy-4,9-androstadiene-3-one which hasthe following formula:

no 0504; 1x

is prepared by the reaction of l7u-trifluoropropynyl-l7/3-hydroxy-5(10)-androstene-3-one, with approximately one equivalent ofbromine in pyridine solution, or with pyridine perbromide hydrobromide.

The 17ot-trifluoropropynyl 17B hydroxy-4,9-androstadiene-3-one isconverted into the 17fl-alkanoyl ester by reaction with an alkanoic acidanhydride or alkanoyl halide in the presence of a tertiary amine such aspyridine, and into the l7fl-alkoxy derivative by reaction with an alkylhalide and silver oxide in a solvent such as dimethylformamide.

The following examples illustrate methods of carrying out the presentinvention but it is to be understood that these examples are given forpurposes of illustration and not of limitation.

Example 1 A 50 cc. three-neck round bottom flask is fitted with aDry-Ice condenser, a dropping funnel and a magnetic stirrer. After theaddition of 210 mg. of magnesium, the entire system is swept withnitrogen and flame dried. Five cc. of dry ether is added to themagnesium and 1 cc. of ethyl bromide in 5 cc. of ether is added dropwisewith stirring over 15 minutes. After all the magnesium has reacted, 5cc. of trifluoropropyne (prepared by the reaction of propiolic acid withsulfur tetrafluoride) is distilled in and refluxed under Dry-Ice-acetonefor one hour. The reaction is then allowed to warm to room temperature,the excess gaseous trifluoropropyne being distilled off. A solution of500 mg. of 3-methoxy-2,5(lO)-androstadiene- 17-one which is dried byazeotropic distillation from benzene, is added in 5 cc. of benzene and 5cc. of dry ether.

The reaction is stirred for 16 hours at room temperature. Water is thenadded and the mixture extracted with ether. The organic extracts arewashed With water until the washings are weakly basic, dried over sodiumsulfate and concentrated in vacuo. The residue is chromatographed on 20g. of basic alumina, by charging with petroleum ether and eluting with amixture of 8 parts petroleum ether and 2 parts ether to give 410 mg. ofl7a-tritluoropropropynyl- 3-methoxy-2,5'( -androstadiene'1 7/3-01.

Example 2 To 150 mg. of the product obtained in Example 1, in cc. ofacetone is added 15 mg. of paratoluenesulfonic acid. This mixture isallowed to stand for 18 hours at room temperature, and is then pouredinto ice water and extracted with ether. The organic extracts are Washedto neutrality with water, dried over sodium sulfate and concentrated invacuo. The residue is chromatographed on 5 g. of acid-washed alumina bycharging with benzene and eluting with 6 parts of a mixture of petroleumether with 4 parts of ether. Recrystallization from a mixture ofpetroleum ether and ether affords 42 mg. of17a-trifiuoropropynyl-l7p-hydroxy 19 nor-4-androstene-3-one, MP. 128-132C.,

LR. A513? 2.95, 4.45, 6.05, 620 U.V. N1 5? 238, 6 15,000; [a]'--21.0CHCL C, 1.0.

Example 3 One-hundred mg. of17a-trifiuoropropynyl-l7B-hydroxy-l9-nor-4-androstene-3-one is heatedwith 1 cc. of acetic anhydride and 1.2 cc. of pyridine on the steam bathovernight. The reaction mixture is then poured onto ice and extractedwith chloroform. The extract is washed with water and concentrated. Theconcentrate is chromatographed over acid-washed alumina and eluted withmixtures of ether and petroleum ether to give 17/3-acetoxy-l7a-tritluoropropynyl-19-nor-4-androstene-3-one.

Example 4 One-hundred mg. of17a-trifiuoropropynyl-17p-hydroxy-l9-nor-4-androstene-3-one is heatedwith 1 cc. of caproyl chloride and 1.2 cc. of pyridine on the steam bathovernight. The reaction mixture is then poured onto ice and extractedwith chloroform. The extract is washed with Water and concentrated. Theconcentrate is chromatographed over acid-washed alumina and eluted withmixtures of ether and petroleum ether to give 17/3-caproyloxy-l7u-trifiuoropropynyl-19-nor-4 androstene-3- one.

Example 5 Example 6 A mixture of 500 mg. of17a-trifluoropropynyl-17fihydroxy-19-nor-4'androstene-3-one, 10 ml. ofdimethylformamide, 20 ml. of methyl iodide, and 1.5 gms. of silver oxideis stirred at room temperature for 4 days, an additional /2 gm. ofsilver oxide being added at the end of each day. One-hundred ml. ofchloroform is then added to the reaction mixture and the mixture isstirred for one hour and filtered. The filtrate is evaporated to drynessand the residual oil is chromatographed over acid-washed alumina andeluted with mixtures of ether 6 and petroleum ether to givel7a-trifluoro-propynyl-17 6* ethoxy-19-nor-4-androstene-3-one.

Example 7 A solution of mg. of17a-trifiuoropropynyl-17phydroxy-19-nor-4-androstene-3-one and 50 mg. ofLindlar catalyst (lead deactivated palladium on a calcium carbonatesupport) in 10 cc. of ethyl acetate is treated With hydrogen until onemole of hydrogen has been absorbed. The mixture is filtered andconcentrated. Chromatography of the crude product yields the(3',3,3-trifluoropropenyl)-17B-hydroxy-19-nor-4 androstene-3-one.

In accordance with the above procedures, but starting with the17,8-methoxyor the17B-acetoxy-17a-trifluoropropynyl-19-nor-4-androstene-3-one in place ofthe 17mtrifluoropropynyl-17,8-hydroxy-l9-non4 androstene-3 -one there isobtained the corresponding 17p-methoxyor the 17,8-acetoxy 17a-(3',3,3'tritluoropropenyl)-19-nor-4- androstene-S-one.

Example 8 A suspension of platinum oxide in 10 cc. of ethanol is reducedand 100 mg. of 17a-trifluoropropynyl-173-hydroxy-l9-nor-4-androstene-3-one is added. Reduction is allowed toproceed until two moles of hydrogen have been absorbed. The solution isfiltered, concentrated and chromtographed on alumina to yield thel7a-(3,3',3'- trifluoropropyl) -17/3-hydroxy-19-nor-4-androstene-3 -one.

In accordance with the above procedures, but starting with the17fl-acetoxyor the 178-methoxy-17a-trifluoropropynyl-19-nor-4-androstene-3-one in place ofthe 170:- trifluoropropynyl-17,8-hydroxy-19-nor 4 androstene-3- onethere is obtained the corresponding 17,8-acetoxyor the17,8-methoxy-17a-(3',3',3'-trifluoropropyl)-19-nor-4- androstene-3-one.

Example 9 To a solution of 100 mg. of 17u-trifluoropropyny1-17B-hydroxy-19-nor-4-androstene-3-one in 3 cc. of dioxane is added 2 cc. ofethyl orthoformate and 10 mg. of ptoluene-sulfonic acid. The reactionmixture is stirred at room temperature for 3 hours and 1 cc. of pyridineis added, followed by the dropwise addition of 5 cc. of water. Theaqueous phase is separated and extracted with benzene. The organicextracts are washed with a sodium bicarbonate solution and then withwater until the washings are neutral. The organic phase is dried oversodium sulfate and concentrated in vacuo to give 3-ethoxy-17atrifluoropropynyl-19-nor-3,5-androstadiene- 1713-01.

In accordance With the above procedures, but starting with the17fi-acetoxyor thel7fl-methoxy-l7a-tlifluoropropynyl-19-nor-4-androstene-3-one in place ofthe 17mtrifluoropropynyl-17fl-hydroxy-l9-nor-4-androstene-3- one thereis obtained as products the corresponding 17;?- acetoxyor the17B-methoxy-3-ethoxy-17a-trifluor0- propynyl-19-nor-3,5-androstadiene.

Example 10 A mixture of 100 mg. ofl7a-trifluoropropynyl-17,B-hydroxy-19-nor-4-androstene-3-one, 0.06 g. of2,4-dinitrobenzenesulfonic acid, 3 ml. of dry dioxane and 0.25 ml. offreshly distilled n-butyl orthoformate are stirred overnight at 30 C.The acid catalyst is then neutralized by addition of 0.1 m1. ofpyridine. The reaction mixture is diluted With water and extracted withether. The combined ether extracts are washed with water, dried andevaporated under reduced pressure. The residue is chromatographed overalumina (alkaline) and diluted with mixtures of ether and petroleumether to separate substantially pure3-n-butoxy-17a-trifluoropropynyl-19- nor-3,5-androstadiene-17,8-01.

In accordance with the above procedures, but starting with the17fl-acetoxyor the-methoxy-17a-trifiuoropropynyl-19-nor-4-androstene-3-one in place of the17atrifluoropropynyl-l7/8-hydroxy-l9-nor 4 androstene-3- 'lowed bydilution with ice water Example 11 A solution consisting of 1 g. of3-ethoxy-l7a-trifiuoropropynyl-19-nor-3,5-androstadiene-17fi-ol, 700 mg.of sodium acetate, 5 ml. of water and 40 ml. of acetone is cooled to C.and 1.07 g. of N bromosuccinimide and 0.33 ml. of acetic acid is added.The mixture is stirred for 3 hours at C. and then poured into water toyield the 6Bbromo17ot-trifiuoropropynyl-17B hydroxy 19-nor-4-androstene-3-one.

Treatment ofofi-bromo-l7or-trifiuoropropynyl-17,6-hydroxyl9-nor-4-androstene-3-one(1.0 g.) with 1.0 g. of lithium bromide, 500 mg. of lithium carbonateand ml. of dimethylformamide for 5 hours at 120 C. foland filtrationaffords 17a-trifluoropropynyl-17B-hydroxy-19-nor-4,6androstadiene-3-one.

A solution consisting of 675 mg. of 170L-ll1lflll01'0-propnyl-17fl-hydroxy-19-nor-4,6-androstadiene 3 one, ml. of 0.2 Nperbenzoic acid dissolved in benzene, and 30 ml. of ether is allowed tostand at room temperature in the dark for 68 hours. The product iswashed with acidified sodium bisulfite solution, water, 2.5 N potassiumhydroxide solution and water. The material is dried and concentrated invacuo.

The crude 6a,7ot-epoxy-17a-trifluoropropynyl-17fihydroxy-19-nor-4-androstene-3-one is used directly in the next step.

The 6a,7ot-epoxy-17a-trifluoropropynyl-17B hydroxy-19-nor-4-androstene-3-one, dissolved in 20 ml. of 0.4 N hydrochloricacid in chloroform, is allowed to stand for 5.5 hours at roomtemperature, and then subsequently poured into iced sodium bicarbonatesolution. The prodnot is extracted with chloroform, dried, andconcentrated in vacuo. Chromatography on acid-washed alumina (20 g.) andelution with ether-petroleum ether mixtures atfords the6-chloro-l7ot-trifluoropropynyl-17/3 hydroxy- 19nor-4,6-androstadiene-3-one.

In accordance with the above procedures, but starting with the176-acetoxyor the17fi-methoxy-3-ethoxy-17octrifluoropropynyl-19-nor-3,5-androstadiene inplace of the S-ethoxy-17a-trifluoropropynyl-19-nor-3,5 androstadienethere is obtained the corresponding 17fi-acetoxyor 17,8-methoxy-6-chloro-17ot-trifluoropropynyl 19 nor 4,6-

androstadiene-Ia-one.

Example 12 To 410 mg. of 17a-trifluoropropynyl-3-methoxy 2,5(10)-androstadiene-17[3-ol in 4.1 cc. of dioxane and 18.45 cc. ofabsolute ethanol is added 8.2 cc. of glacial acetic acid in 4.1 cc. ofwater. This reaction mixture -is left stirring at room temperature for 5hours. It is then poured into an ice-sodium bicarbonate solution andextracted with benzene. The benzene extract is washed with water untilthe washings are just slightly basic, dried over sodium sulfate andconcentrated in vacuo. The crude product (344 mg.) is chromatographed on13 g. of neutral (ethyl acetate washed) alumina by charging with amixture of 1 part benzene and 1 part petroleum ether, and eluting withmixtures of 8 parts petroleum ether:2 parts ether and 7 parts petroleumether:3 parts ether. Recrystallization from a mixture of ether-petroleumether afiords 167 mg. of 17a-trifluoropropyny1-17B-hydroxy-19-nor-5(10)androstene 3 one, M1. 137 140 C.,

LR. REE; 2.92, 4.51, 5.8-5.85, 6.01, 7.85, 8.68.85 t

[ 113 G-I10.1 dioxane, C, 1.0.

Calculated for 21H25O2F c, 68.85; H, 6.88; F, 15.56.

Found: C, 68.77; H, 7.00; F, 17.3.

5(10) androstene-3-one in 5 cc. of pyridine is added one equivalent ofbromine. The reaction is stirred for two hours at room temperature,poured into ice-water and extracted with ether. The ether extract iswashed with water, dried over sodium sulfate, and concentrated in vacuoto yield 17a-triiluoropropyny1-17B-hydroxy-19-nor-4,9-androstadiene-3-one.

Example 14 One-hundred mg. of 17a-trifluoropropynyl-17Bhydroxy-19-nor-4,9-androstadiene-3-one is heated with 1 cc. 01": aceticanhydride and 1.2 cc. of pyridine on the steam bath overnight. Thereaction mixture is then poured onto ice and extracted with chloroform.The extract is washed with Water and concentrated. The concentrate ischromatographed over acid-washed alumina and eluted with mixtures ofether and petroleum ether to give17B-acetoxy-l7t-trifluoropropynyl19-nor-4,9 androstadiene 3- one.

Example 15 A mixture of 500 mg. of17ot-triiiuoropropynyl-17,8-hydroxy-l9-nor-4,9-androstadiene-3-one, 10ml. of dimethyltormamide, 20 ml. of methyl iodide, and 1.5 gms. ofsilver oxide is stirred at room temperature for 4 days, an additional /2gm. of silver oxide being added at the end of each day. One-hundred ml.of chloroform is then added to the reaction mixture and the mixture isstirred for one hour and filtered. The filtrate is evaporated to drynessand the residual oil is chromatographed over acid-washed alumina "andeluted with mixtures of ether and petroleurn ether to give17et-trifluoropropynyl-17,8-metlroxy-19- nor-4,9-anclrostadiene-3-one.

Various changes and modifications may be made in carrying out thepresent invention without departing from the spirit and scope thereof.Insofar as these changes and modifications are Within the purview of theannexed claims, they are to be considered as part of our invention.

We claim:

1. 17oz trifluoropropynyl 3 methoxy 2,5( 10) androstadiene 17B ol.

2. 17a trifluoropropynyl 17B hydroxy 5(10) androstene 3 one.

3.' 17a trifiuoropropynyl 175 hydroxy 19 nor- 4 androstene 3 one.

4. 17,9 acetoxy 17a trifluoropropynyl 19 nor 4- androstene 3 one.

5. 17 ,8 caproyloxy 17oz trifiuoropropynyl 19 nor- 4 androstene 3 one.

6. 17a trifluoropropyny-l 17,8 methoxy 19 -nor- 4 androstene 3 one.

7. 17,3 ethoxy 17oz trifiuoropropynyl 19 nor 4- androstene 3 one.

8. A compound selected from the group consisting of 17a (3,3',3'trifluoropropenyl) 176 hydroxy 19- nor 4 androstene 3 one and the17fi-alkoxy ethers and 17B-alkanoyl esters thereof.

9. A compound selected from the group consisting of 1701. (3',3',3't-rifiuoropropyl) 175 hydroxy 19 nor- 4 androstene 3 One and the17,3-alkoxy ethers and 17 3-alkanoyl esters thereof.

10. A compound selected from the group consisting of 3 alkoxytrifluoropropynyl 19 nor 3,5 an- .drostadiene 17B 01 and the 17fl-alkoxyethers and the 17/3'alkan0y1 esters thereof.

11. 3 ethoxy 17 a trifluoropropynyl 19 nor 3,5- androstadiene 1719 01.

12. 3 butoxy 17a trifluoropropynyl 19 nor 3,5- androstadiene 17B 01. i

13. 6,3 bromo 17a trifluoropropynyl 1713 hydroxy 19 nor 4 androstene 3one.

14. 17a triflnoropropynyl 17B hydroxy 19 -nor- 4,6 androstadiene 3 one.

15. 6a,7u epoxy 17a trifluoropropynyl 1713 hydroxy 19 nor- 4 androstene3 one.

16. A compound selected from the group consisting of 6 chloro 17atrifluoropropynyl 17 8 hydroxy- 19 nor 4,6 androstadiene 3 one and thel7fi-alkoxy others and the 17,8-alkanoyl esters thereof.

17. A compound selected from the group consisting of 17atrifluoropropynyl 17c hydroxy 19 nor 4,9- androstadiene 3 one and the17pI-alkoXy ethers and the 17/8-alkanoyl esters thereof.

18. Process for the preparation of 170: trifluoropropynyl 3 methoxy 2,5(10) androstadiene 175 which comprises reacting 3 methoxy 2,5()androstadiene-17-one with trifiuoropropyne which has been previouslytreated with magnesium ethyl bromide.

19. Process for the preparation of 170: trifiuoropropynyl 175 hydroxy 19nor 4 androstene 3 one which comprises reacting 17a trifluoropropynyl 3-methoxy 2,5 10) androstadiene 17/3 01 with a strong acid.

20. Process for the preparation of 3 alkoxy 17oz -trifiuoropropynyl 19nor 3,5 androstadiene 17,8 01 which comprises reacting 17oztrifluoropropynyl 17,8- hydroxy l9 nor 4 androstene- 3 one with an alkylorthoformate in dioxane solution in the presence of a strong acidcatalyst.

21. Process for the preparation of 17/3 alkanoyloxy- 17o:trifiuoropropynyl 19 nor 4 androstene 3 one which comprises reacting 17atrifluoropropynyl 17/8- hydroxy 19 nor 4 androstene 3 one with a cornpound selected from the group consisting of alkanoyl acid anhydrides andalkanoyl halides in the presence of a tertiary amine.

22. Process for the preparation of 17a trifluoropropynyl 17,8 alkoxy 19nor 4 androstene 3- one which comprises reacting a solution of 17mtrifluoropropynyl 17,8 hydroxy 19 nor 4 androstene 3 one in an organicsolvent with an alkyl halide and silver oxide. 23. Process for thepreparation of 6 8 bromo 17atrifluoropropynyl 175 hydrcXy 19 nor 4androstene-3-one which comprises reacting a solution of17atrifluoropropynyl 1Z8 hydroxy 19 nor 4 androstene-S-one in an organicsolvent with N-brcmosuccinimide in the presence of acetic acid andsodium acetate.

24. Process for the preparation of 17a trifluoropro pynyl 17,8 hydroxyl9 nor 4,6 androstadiene 3- one comprising heating a solution of 6Bbromo 17atrifiuoropropynyl 17$ hydroxy l9 nor 4 androstene-3-one in anorganic solvent with lithium bromide and lithium carbonate.

25. Process for the preparation of :,70: epoxy 17mtrifluoropropynyl 17 8hydroxy 19 nor 4 androstene 3 one comprising oxidizing atrifiuoropropynyl 17,8 hydroxy 19 nor 4,6 androstadiene 3- one withperbenzoic acid.

26. Process for the preparation of 6 chloro 17atrifiucropropynyl 17Ehydroxy 19 nor 4,6 androst adiene-3 one comprising treating a solutionof 600,70:- epoxy 17a trifluoropropynyl 17,6 hydroxy 19 -nor- 4androstene 3 one with hydrogen chloride.

27. Process for the preparation of 170; trifluoropropynyl 17/3 hydroxy5(10) androstene 3 one which comprises reacting 17a trifiuoropropynyl 3methoXy- 2,5(10) androstadiene 17,8 01 with a Weak acid.

28. Process for the preparation of 17cc trifluoropropynyl 17B hydroXy 19nor 4,9 androstadiene 3- one which comprises treating 17atrifluoropropynyl- 17 3 hydroxy 5(10) androstene 3 one withapproximately one equivalent weight of bromine in pyridine solution.

References Cited in the file of this patent Journal of the AmericanChemical Society, March 5, 1960, vol. 82, pages 12304235, Knox et al.

Journal Chemical Society, June 1960, pages 2389-2391, Ellis et al.

1. 17A - TRIFLUOROPROPYNYL -3- METHOXY - 2,5(10) - ANDROSTADIENCE -17B - OL.
 19. PROCESS FOR THE PREPARATIN OF 17A - TRIFLUOROPROPYNYL -17B - HYDROXY - 19 - NOR - 4 - ANDROSTENE - 3 - ONE WHICH COMPRISESREACTING 17A - TRIFLUOROPROPYNYL - 3METHOXY - 2,5(10) - ANDROSTADIENE -17B - OL WITH A STRONG ACID.